Conventionally, invasive methods such as subconjunctival or intravitreal injections are widely used for drug treatments for diseases in the posterior segment of the eye.
This is partly because topical administration to the eye, such as instillation, results in a short drug residence time due to tears and the like, or results in low drug permeability into corneal and conjunctival epithelial cells.
However, there are problems with injections such as a lack of ease of administration, and concerns about complications such as vitreous hemorrhage and retinal detachment. Hence, there is a need for a drug that is highly capable of being delivered to the posterior segment of the eye via non-invasive methods of administration, such as local administration to the eye.
Several attempts have been made to utilize liposomes for local administration to the eye; however, such attempts have been made solely for the purpose of extending residence time on the corneal surface (Patent Literature 1), and the like. Thus, there have been no successful results for delivery of a drug to the posterior segment of the eye by local administration of a liposome to the eye.
Patent Document 2 discloses a liposome preparation intended for delivery into the retinal cells, reporting that the “DNA encapsulated” in a specific liposome containing dilauroylphosphatidylcholine (DLPC) or dioleoylphosphatidylethanolamine (DOPE) could be delivered to the retinal ganglion cells. This liposome, however, does not encapsulate a chemical substance.
The “Detailed Description of the Invention” section of Patent Document 2 discloses various liposome compositions and preparation methods. However, among the liposomes containing phospholipids, those that were actually demonstrated to deliver the encapsulated DNA to the retinal ganglion cells were all multilamellar liposomes (multilamellar vesicles; hereinafter abbreviated as “MLVs”).
As a result of unique research and development conducted by the present inventors, it has become evident that, in the case of MLVs, the liposome itself cannot be delivered to the posterior segment of the eye. That is, in Patent Document 2, although the DNA encapsulated in the liposome was delivered to the posterior segment of the eye, it is likely that the liposome itself collapses midway, and does not reach the posterior segment of the eye. This means that the proportion of the encapsulated DNA that was delivered to the posterior segment of the eye is not necessarily high.
Patent Document 1: Japanese Patent No. 3,624,418
Patent Document 2: Japanese Patent No. 3,963,506